RRC ID |
44277
|
著者 |
Obara G, Toyohira Y, Inagaki H, Takahashi K, Horishita T, Kawasaki T, Ueno S, Tsutsui M, Sata T, Yanagihara N.
|
タイトル |
Pentazocine inhibits norepinephrine transporter function by reducing its surface expression in bovine adrenal medullary cells.
|
ジャーナル |
J Pharmacol Sci
|
Abstract |
(±)-Pentazocine (PTZ), a non-narcotic analgesic, is used for the clinical management of moderate to severe pain. To study the effect of PTZ on the descending noradrenergic inhibitory system, in the present study we examined the effect of [(3)H]norepinephrine (NE) uptake by cultured bovine adrenal medullary cells and human neuroblastoma SK-N-SH cells. (-)-PTZ and (+)-PTZ inhibited [(3)H]NE uptake by adrenal medullary cells in a concentration-dependent (3-100 μM) manner. Eadie-Hofstee analysis of [(3)H]NE uptake showed that both PTZs caused a significant decrease in the V(max) with little change in the apparent K(m), suggesting non-competitive inhibition. Nor-Binaltorphimine and BD-1047, κ-opioid and σ-receptor antagonists, respectively, did not affect the inhibition of [(3)H]NE uptake induced by (-)-PTZ and (+)-PTZ, respectively. PTZs suppressed specific [(3)H]nisoxetine binding to intact SK-N-SH cells, but not directly to the plasma membranes isolated from the bovine adrenal medulla. Scatchard analysis of [(3)H]nisoxetine binding to SK-N-SH cells revealed that PTZs reduced the B(max) without changing the apparent K(d). Western blot analysis showed a decrease in biotinylated cell-surface NE transporter (NET) expression after the treatment with (-)-PTZ. These findings suggest that PTZ inhibits the NET function by reducing the amount of NET in the cell surface membranes through an opioid and σ-receptor-independent pathway.
|
巻・号 |
121(2)
|
ページ |
138-47
|
公開日 |
2013-1-1
|
DOI |
10.1254/jphs.12164fp
|
PII |
DN/JST.JSTAGE/jphs/12164FP
|
PMID |
23370666
|
MeSH |
Adrenal Medulla / diagnostic imaging
Adrenal Medulla / drug effects
Adrenal Medulla / metabolism
Analgesics, Opioid / pharmacology*
Animals
Cattle
Cell Line
Cell Membrane / diagnostic imaging
Cell Membrane / drug effects
Cell Membrane / metabolism
Cells, Cultured
Ethylenediamines / pharmacology
Fluoxetine / analogs & derivatives
Fluoxetine / pharmacology
Gene Expression / drug effects
Humans
Naltrexone / analogs & derivatives
Naltrexone / pharmacology
Narcotic Antagonists / pharmacology*
Norepinephrine / metabolism
Norepinephrine Plasma Membrane Transport Proteins / antagonists & inhibitors*
Norepinephrine Plasma Membrane Transport Proteins / metabolism*
Pentazocine / pharmacology*
Radionuclide Imaging
|
IF |
2.835
|
引用数 |
6
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
|
リソース情報 |
ヒト・動物細胞 |
COS-7(RCB0539)
SK-N-SH(RCB0426) |